WO2020017619A1 - Virus inactivating agent - Google Patents

Virus inactivating agent Download PDF

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Publication number
WO2020017619A1
WO2020017619A1 PCT/JP2019/028379 JP2019028379W WO2020017619A1 WO 2020017619 A1 WO2020017619 A1 WO 2020017619A1 JP 2019028379 W JP2019028379 W JP 2019028379W WO 2020017619 A1 WO2020017619 A1 WO 2020017619A1
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Prior art keywords
oil
virus
inactivating agent
virus inactivating
agent according
Prior art date
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PCT/JP2019/028379
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French (fr)
Japanese (ja)
Inventor
翔子 有野
裕人 白神
有喜子 蛭間
Original Assignee
株式会社 資生堂
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by 株式会社 資生堂 filed Critical 株式会社 資生堂
Priority to CN201980047026.2A priority Critical patent/CN112423771B/en
Priority to EP23155268.8A priority patent/EP4205755A1/en
Priority to JP2020531373A priority patent/JP7376480B2/en
Priority to EP19836963.9A priority patent/EP3824896A4/en
Priority to US17/261,263 priority patent/US20210275434A1/en
Publication of WO2020017619A1 publication Critical patent/WO2020017619A1/en
Priority to US18/117,618 priority patent/US20230201104A1/en
Priority to JP2023118876A priority patent/JP2023139155A/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/718—Starch or degraded starch, e.g. amylose, amylopectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/534—Mentha (mint)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/06—Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/31—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/362—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41—Amines
    • A61K8/416—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/731—Cellulose; Quaternized cellulose derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/732—Starch; Amylose; Amylopectin; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Definitions

  • the present invention relates to peppermint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, cajeput oil, niau cineole oil, lime oil, lemon oil, lemon verbena oil, One selected from the specific essential oils of St. John's wort oil, Rabinzala oil, Rosewood oil, Melissa / Lemon balm oil, Myrrh oil, Mandarin oil, Vetiver oil, Frankincense oil, Citronella oil, Cardamom oil, Angelica oil, and cationized starch Alternatively, the present invention relates to a virus inactivating agent containing two or more kinds as an active ingredient, and an external preparation for skin containing the virus inactivating agent.
  • Extracts in particular, some of the essential oils extracted from aromatic substances contained in plant extracts have an inactivating effect on various viruses including influenza virus.
  • "Essential oil” essential oil
  • Extraction methods, compression methods, and the like are known as methods for extracting natural flavors, and flavors obtained by the compression method are sometimes referred to as essential oils (Non-Patent Document 1).
  • raspberry (Rubus idaeus), strawberry (Fragaria vesca ⁇ ), blackberry (Rubus fruticosus), fig (Ficus carica), akaza (Cenopodium at at at at u u u u u m u m ri ri m ⁇ ⁇ ) , Apples (Malus pumila ⁇ ), violets (Viola odorata), kuromoji (Lindera umbellata), guarana (Paullinia cupana), Butteria ⁇ fusicinaris, tsuyuna (Communis) Zuna (Capsella bursapastoris), Enmeisou (Rabdosia japonica), Wild Strawberry (Fragaria v esca), Hoahaundo (Marrubium vulgare), Marsh mallow (Althaea officinalis), plantain (Plantago asiatica), lemon verbena (Aloysi
  • Patent Literature 2 discloses that an essential oil component obtained by steam distillation of Houttuynia ⁇ cordata ⁇ Thunbo has an inactivating effect on influenza virus, herpes simplex virus type 1 (HSV-1), AIDS virus (HIV) and the like.
  • Patent Document 3 describes that an essential oil extract of patchouli (Pogostemon @ cablin @ Benth.) Has an influenza virus inactivating effect.
  • non-terpene compounds such as n-decylaldehyde, n-dodecylaldehyde and methyl n-nonyl ketone contained in essential oil components are specified as active ingredients in Patent Document 2, and the active ingredient in Patent Document 3 is patchouli. Is extracted with alcohol or n-hexane, and then fractionated to obtain patchouli alcohol (patchol).
  • Patent Document 4 discloses that an extract of fir leaves (fir essential oil) is useful as an anti-influenza virus agent, but the essential oil contains at least 30% by mass of bornyl acetate. It is said that it is preferable that the total amount of added camphene, pinene and limonene be 90% by mass or more based on the total amount of the fir essential oil.
  • Patent Document 5 reports that terpene derivatives such as pinenes, phenols such as eugenol, and sandalwood oil have an inactivating effect on pathogenic membrane viruses such as measles virus.
  • Patent Document 6 a quaternary ammonium cation containing silicon, such as dimethyloctadecyl [3- (triethoxysilyl) propyl] ammonium chloride (EtAC), is safe as a mouthwash such as a denture cleaner. It has also been reported that it has the ability to inactivate viruses such as influenza virus and norovirus (Patent Document 6). However, Patent Document 6 suggests that a slight difference in the structure of the quaternary ammonium cation may cause a problem in antiviral effect and stability (paragraphs 0008 and 0009).
  • EtAC dimethyloctadecyl [3- (triethoxysilyl) propyl] ammonium chloride
  • the present invention has been made in view of the current situation in which, in the above technical situation, not only bacteria and viruses but also stimulants that can adversely affect the skin, such as pollen and air pollutants such as PM2.5, are increasing. It is an object of the present invention to provide a virus inactivating agent exhibiting an effect in such an amount that does not cause skin irritation, and a skin external preparation composition containing the virus inactivating agent.
  • the present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, blending one or more of essential oils extracted from a specific plant and / or cationized starch as an active ingredient, The present inventors have found that the present invention exhibits a safe and excellent virus inactivating effect without irritation, thereby completing the present invention.
  • the present invention includes the following.
  • a virus inactivating agent comprising two or more types.
  • the virus inactivating agent according to the above-mentioned [2] which contains mint oil, eucalyptus oil, rosemary oil, and sage oil as active ingredients.
  • the virus inactivating agent according to the above [1] which comprises a cationized starch as an active ingredient.
  • Virus inactivator [11] The virus inactivating agent according to any one of [1] to [10], wherein the virus is a single-stranded RNA virus having an envelope. [12] The virus inactivating agent according to [11], wherein the enveloped single-stranded RNA virus is a virus belonging to the orthomyxoviridae family. [13] The virus inactivating agent according to the above [12], wherein the virus belonging to the orthomyxoviridae family is an influenza virus. [14] A skin external preparation composition comprising the virus inactivating agent according to any one of [1] to [13]. [15] The skin external preparation composition according to the above [14], further comprising an alcohol. [16] The composition for external use on skin according to the above [15], wherein the content of the alcohol is 50% by mass or less.
  • the virus inactivating agent of the present invention preferably, by combining a plurality of essential oils having a low limonene content to make the total amount of limonene a predetermined amount or more, an excellent virus inactivating effect is produced without causing skin irritation. . Further, the virus inactivating agent of the present invention exhibits an excellent virus inactivating effect by blending a naturally derived component called cationized starch. Therefore, the skin external preparation composition containing the virus inactivating agent of the present invention has an advantage of having a virus inactivating effect safely and easily.
  • One embodiment of the virus inactivating agent of the present invention comprises one or more plant extracts as an active ingredient, and the plant extracts are selected from the group consisting of mint (Lamiaceae, mint) and (Lumaria eucalyptus). ) Eucalyptus, (Lamiaceae Mannenlow) Rosemary, (Lamiaceae L. spp.) Sage, (Lamiaceae L. spp.) Tea Tree, (Zingiberaceae Hanamyoga) L.
  • John's wort (Camphoraceae Nikkei) Labins La, (Fabaceae, Crassaceae) Rosewood, (Lamiaceae, Laminariaceae) Melissa / Lemon balm, (Orchidaceae, Commiphora) Myrrh, (Rutaceae, Citrus) Mandarin, (Poaceae, Oleraceae) Vetiver, (Kanran)
  • the plant is characterized by being derived from a plant selected from the group consisting of the family Boswellia frankincense, (Poaceae Ogarkaya) Citronella, (Zingiberaceae Zygium) cardamom, and (Ceramiaceae Sisudo) genus Angelica.
  • essential oil extracted as an aromatic substance contained in the above-mentioned plant is preferable.
  • essential oil essential oil
  • an oil component extracted from a plant by another method such as an extraction method or a squeezing method is also included in the “essential oil” in the present invention as long as it contains an essential oil component (such as an aromatic substance).
  • solvent extraction methods alcohol extraction method, organic solvent extraction method, etc.
  • an oil / fat adsorption extraction method digestion method or cold immersion method
  • supercritical fluid extraction method a solvent extraction method is often used.
  • Solvents used for the extraction are not limited, but include, for example, alcohols such as ethanol, methanol, propanol, isopropanol, and butanol, and organic solvents including relatively high-polarity solvents such as acetone to low-polarity solvents such as hexane. Is exemplified.
  • the "essential oil” in the present invention is obtained by further purifying and concentrating the oil obtained by the above method using various purification techniques such as hydrophobic beads or adsorption chromatography using a carrier such as porous beads, silica gel or alumina. It may be something.
  • essential oil obtained from each of the plants listed in paragraph 0015 is referred to as peppermint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, respectively.
  • Kajupte oil Niauli Cineol oil, Lime oil, Lemon oil, Lemon verbena oil, St. John's wort oil, Rabinzala oil, Rosewood oil, Melissa / Lemon balm oil, Myrrh oil, Mandarin oil, Vetiver oil, Frankincense oil, Citronella oil, Called cardamom oil and angelica oil.
  • the virus inactivating agent of the present invention includes peppermint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, cajeput oil, niau cineole oil, lime oil, and lemon oil.
  • Essential oil selected from the group consisting of, lemon verbena oil, St. John's wort oil, Rabinzala oil, rosewood oil, melissa / lemon balm oil, myrrh oil, mandarin oil, vetiver oil, frankincense oil, citronella oil, cardamom oil, and angelica oil
  • it contains two, more preferably three, even more preferably four or more essential oils.
  • a preferred embodiment of the virus inactivating agent of the present invention comprises two, preferably three, and more preferably four as active ingredients selected from the group consisting of peppermint oil, eucalyptus oil, rosemary oil, and sage oil. I do.
  • the virus inactivating agent of the present invention is preferably combined with the essential oil so that the content of limonene contained in the essential oil to be blended is 0.006% by mass or more based on the total amount of the virus inactivating agent. preferable. If the amount of limonene is less than 0.006% by mass, a sufficient virus inactivating effect cannot be obtained.
  • Perimonene is a monocyclic monoterpene hydrocarbon mainly contained in the citrus peel.
  • Limonene is a main component of essential oils obtained from citrus fruits such as oranges and lemons, but limonene contained in orange peel oil and lemon oil is D-form, and limonene contained in peppermint oil and the like is L-form.
  • the limonene used in the present invention may be a D-form, an L-form or a mixture of a D-form and an L-form (a racemic body or the like), and is not particularly limited.
  • the virus inactivator of the present invention has an embodiment containing D-limonene of 0.006% by mass or more, an embodiment containing L-limonene of 0.006% by mass or more, and a total of D-limonene and L-limonene.
  • the embodiment containing 0.006% by mass or more is included.
  • the upper limit of the amount of limonene is not particularly limited, but is usually 0.05% by mass or less, preferably 0.04% by mass or less, 0.03% by mass or less, or 0.02% by mass or less. Excessive amounts of limonene may cause skin irritation.
  • the amount of limonene relative to the total amount of essential oil to be blended is preferably less than 5 g, preferably less than 4.5 g, per 100 g of essential oil.
  • Cationized starch is a cationic polymer obtained by introducing a cationic group such as quaternary ammonium into starch having a basic skeleton of a structure in which a plurality of glucoses are bonded via ⁇ -1,4-glucosidic bonds.
  • the cationized starch used in the present invention includes the following formula (I):
  • the cationic polymer represented by is preferred.
  • X - is an anion derived from inorganic or organic acids.
  • the inorganic acid include hydrochloric acid, sulfuric acid, and nitric acid
  • examples of the organic acid include carboxylic acid such as acetic acid.
  • the anion X ⁇ in the above formula (I) is preferably a halide ion, particularly Cl ⁇ .
  • a and b represent the number of each monomer in the polymer and the ratio of each monomer.
  • the average molecular weight (weight average molecular weight: Mw) of the cationized starch represented by the formula (I) is preferably 30,000 to 1,000,000, and more preferably 100,000 to 500,000.
  • the cationized starch represented by the formula (I) is “hydroxypropyltrimonium chloride starch” under the cosmetic ingredient designation.
  • Commercially available products under the display name include, for example, “Sensormer CI-50” (manufactured by NALCO Performance Products), “DOCCARCHCH CP” (manufactured by DOC Japan), “Amilomer 25L” (manufactured by Graef Chemie), “ “Amilomer 50M” (manufactured by Graefe Chemie), “Famar MS5940” (manufactured by Corn Products International), "Exel FM-004" (manufactured by Nippon Starch Co., Ltd.) and the like can be used, and these commercially available products can be used.
  • Cationized starch is mainly used as a hair conditioning agent as a cationic polymer together with cationized cellulose, polyquaternium and the like, but it has been surprisingly discovered by the present invention that cationized starch has a virus inactivating effect for the first time. It is an important finding.
  • the amount of the cationized starch in the virus inactivating agent of the present invention is 0.1% by mass or more, preferably 0.15% by mass or more, more preferably 0% by mass or more, based on the total amount of the virus inactivating agent. 0.2 mass% or more. If the amount is less than 0.1% by mass, a sufficient virus inactivating effect cannot be obtained.
  • the upper limit of the amount of the cationized starch is not particularly limited, but is usually 5% by mass or less, preferably 3% by mass or less, more preferably 2% by mass or less.
  • virus inactivation means removing or significantly reducing the ability of a virus to infect or proliferate.
  • the virus that can be inactivated by the virus inactivating agent of the present invention is not particularly limited, and various viruses can be inactivated regardless of the type of genome, the presence or absence of an envelope, and the like.
  • influenza A, B, influenza C isavirus, quaranja virus, togotovirus, rhinovirus, poliovirus, rotavirus, norovirus, enterovirus, hepatovirus, astrovirus, sapovirus, hepatitis E virus, Parainfluenza virus, mumps virus, measles virus, human metapneumovirus, respiratory syncytial virus, nipavirus, Hendra virus, yellow fever virus, dengue virus, Japanese encephalitis virus, West Nile virus, type B, hepatitis C virus, eastern and western horses Encephalitis virus, rubella virus, Lassa virus, Junin virus, Machupo virus, Guanarito virus, monster virus, Crimean Congo hemorrhagic fever virus, Hanta virus, Shinnonbrewi Virus, rabies virus, Ebola virus, Marburg virus, bat lyssa virus, human T cell leukemia virus, human immunodeficiency virus, human coronavirus, S
  • the virus inactivating agent of the present invention includes peppermint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, cajeput oil, niau cineole oil, lime oil, and lemon oil.
  • Essential oil selected from the group consisting of, lemon verbena oil, St.
  • John's wort oil, Rabinzala oil, rosewood oil, melissa / lemon balm oil, myrrh oil, mandarin oil, vetiver oil, frankincense oil, citronella oil, cardamom oil, and angelica oil A sufficient effect can be obtained by blending one or more of the above, or a cationized starch alone, but a virus inactivating agent may be used as an active ingredient by combining an essential oil and a cationized starch.
  • the present invention provides a skin external preparation composition containing the above virus inactivating agent.
  • the "skin external preparation composition” of the present invention may be any external preparation composition applied to the skin (including the scalp), and includes, for example, cosmetics (including basic cosmetics and makeup cosmetics), cleaning agents, It can include external medicines, quasi-drugs, and the like.
  • the skin external preparation composition of the present invention may be in the form of the above-described virus inactivating agent alone, or may be in a form in which various components generally used in the skin external preparation composition are appropriately blended as necessary.
  • the skin external preparation composition of the present invention may contain a lower alcohol such as ethanol (an alcohol having 6 or less carbon atoms). It is known that lower alcohols such as ethanol have an inactivating effect on various viruses including influenza virus, and a virus inactivating agent composition containing a high amount of alcohol is also known.
  • the blending amount when the alcohol is blended is preferably 50% by mass or less, preferably 40% by mass or less, or 30% by mass or less. Sensitive skin can also be used with confidence.
  • oils animal and vegetable oils, mineral oils, ester oils, wax oils, silicone oils, higher alcohols, phospholipids, fatty acids, etc.
  • Surfactants anionic, cationic, amphoteric or nonionic surfactants
  • vitamins vitamin A group, vitamin B group, folic acid, nicotinic acid, pantothenic acid, biotin, vitamin C group, vitamin D group , Vitamin E group, other ferulic acid, ⁇ -oryzanol, etc.
  • ultraviolet absorbers p-aminobenzoic acid, anthranil, salicylic acid, coumarin, benzotriazole, tetrazole, imidazoline, pyrimidine, dioxane, furan, pyrone, camphor, nucleic acid, Allantoin and their derivatives, amino acid compounds, shikonin, baicalin, ba Kalein, berberine, etc.
  • antioxidants e.g., stearic acid, etc.
  • the dosage form of the skin external preparation composition of the present invention is arbitrary, and examples thereof include lotions, creams, ointments, emulsions, foundations, oils, packs, soaps (including medicated soaps), body soaps, lipsticks, perfumes, and facial cleansers. , Deodorant (armpit odor, foot odor, etc.), bath agent, shampoo, conditioner, hair tonic, hair spray and the like.
  • the form of the skin external preparation composition of the present invention can be in the form of a solution, cream, paste, gel, gel, foam, solid, or powder, depending on the dosage form.
  • the skin external preparation composition of the present invention can be prepared by using the above-described virus inactivating agent as an essential component according to a usual method depending on the dosage form and form.
  • Example 1 Inactivating effect on influenza virus (1)
  • Sample (Test Solution) A sample (test solution) of a virus inactivating agent was prepared according to the formulation shown in Table 1 below.
  • Test method Influenza virus type A (H1N1 / PR / 8/34) strain was used as a test virus strain. 0.12 mL (1 ⁇ 10 4 pfu / mL) of the virus solution was added to 1.080 mL of each sample (test solution) shown in Table 1, and after reacting for 30 minutes, serially diluted 10-fold with SCDLP medium, and 96 wells were previously prepared. Canine kidney cells (MDCK) cultured on the plate were inoculated, cultured at 37 ° C. under 5% CO 2 , the number of plaques formed was measured, and the residual virus infectious titer was determined.
  • MDCK Canine kidney cells
  • Example 2 Inactivation effect on influenza virus (part 2) 1) Preparation of Sample (Test Solution) A sample (test solution) of a virus inactivating agent was prepared according to the formulation shown in Table 3 below.
  • An antiviral mist was obtained by discharging the skin external preparation of Formulation Example 1 using a mist-like dispenser.
  • this formulation may be used as a stock solution, and an aerosol product may be prepared by using a compressed gas (nitrogen, LPG, carbonic acid, etc.) as appropriate.

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Abstract

The purpose of the present invention is to provide: a virus inactivating agent that exhibits an effect at an amount that does not cause skin irritation; and an external skin preparation composition containing said virus inactivating agent. The present invention relates to: a virus inactivating agent containing, as an effective component thereof, at least one selected from mint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, shell ginger oil, peppermint oil, lemongrass oil, cajeputi oil, niaouli cineole oil, lime oil, lemon oil, lemon verbena oil, St. John's wort oil, ravintsara oil, rosewood oil, Melissa/lemon balm oil, myrrh oil, mandarin oil, vetiver oil, frankincense oil, citronella oil, cardamom oil, Angelica oil, and cationized starch; and an external skin preparation composition containing the same.

Description

ウイルス不活化剤Virus inactivator
　本発明は、ハッカ油、ユーカリ油、ローズマリー油、セージ油、ティーツリー油、月桃油、ペパーミント油、レモングラス油、カユプテ油、ニアウリ・シネオール油、ライム油、レモン油、レモンバーベナ油、セントジョーンズワート油、ラビンツァラ油、ローズウッド油、メリッサ/レモンバーム油、ミルラ油、マンダリン油、ベチバー油、フランキンセンス油、シトロネラ油、カルダモン油、アンジェリカ油という特定の精油、およびカチオン化デンプンから選ばれる１種または２種以上を有効成分として含有するウイルス不活化剤、および該ウイルス不活化剤を含有する皮膚外用剤組成物に関する。 The present invention relates to peppermint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, cajeput oil, niau cineole oil, lime oil, lemon oil, lemon verbena oil, One selected from the specific essential oils of St. John's wort oil, Rabinzala oil, Rosewood oil, Melissa / Lemon balm oil, Myrrh oil, Mandarin oil, Vetiver oil, Frankincense oil, Citronella oil, Cardamom oil, Angelica oil, and cationized starch Alternatively, the present invention relates to a virus inactivating agent containing two or more kinds as an active ingredient, and an external preparation for skin containing the virus inactivating agent.
　インフルエンザウイルスをはじめとする様々なウイルスに対して、植物抽出物、特に植物抽出物中に含まれる芳香物質を抽出した精油の一部が不活化効果を示すことが知られている。「精油（エッセンシャルオイル）」は、化粧料における天然香料の一種であり、狭義には、植物またはその乾燥物から水蒸気蒸留して得られた油分である。天然香料の採油法としては、抽出法、圧搾法等が知られており、圧搾法で得られた香料をエッセンシャルオイルと呼ぶ場合もある（非特許文献１）。 植物 It is known that plant extracts, in particular, some of the essential oils extracted from aromatic substances contained in plant extracts have an inactivating effect on various viruses including influenza virus. "Essential oil" (essential oil) is a kind of natural fragrance in cosmetics, and in a narrow sense, is an oil component obtained by steam distillation from a plant or a dried product thereof. Extraction methods, compression methods, and the like are known as methods for extracting natural flavors, and flavors obtained by the compression method are sometimes referred to as essential oils (Non-Patent Document 1).
　例えば、ラズベリー（Ｒｕｂｕｓ　ｉｄａｅｕｓ）、ストロベリー（Ｆｒａｇａｒｉａ　ｖｅｓｃａ ）、ブラックベリー（Ｒｕｂｕｓ　ｆｒｕｔｉｃｏｓｕｓ）、イチジク（Ｆｉｃｕｓ　ｃａｒｉｃａ）、アカザ（Ｃｈｅｎｏｐｏｄｉｕｍ　ａｌｂｕｍ）、アグリモニー（Ａｇｒｉｍｏｎｉａ　ｅｕｐａｔｏｒｉａ）、ユーカリ（Ｅｕｃａｌｙｐｔｕｓ　ｇｌｏｂｕｌｕｓ）、モモ（Ｐｒｕｎｕｓ　ｐｅｒｓｉｃａ）、リンゴ（Ｍａｌｕｓ　ｐｕｍｉｌａ ）、ヴァイオレット（Ｖｉｏｌａ　ｏｄｏｒａｔａ）、クロモジ（Ｌｉｎｄｅｒａ　ｕｍｂｅｌｌａｔａ）、ガラナ（Ｐａｕｌｌｉｎｉａ　ｃｕｐａｎａ）、ワタフジウツギ（Ｂｕｄｄｌｅｉａ　ｏｆｆｉｃｉｎａｌｉｓ）、ツユクサ（Ｃｏｍｍｅｌｉｎａ　ｃｏｍｍｕｎｉｓ）、ナズナ（Ｃａｐｓｅｌｌａ　ｂｕｒｓａｐａｓｔｏｒｉｓ）、エンメイソウ （ Ｒａｂｄｏｓｉａ　ｊａｐｏｎｉｃａ）、ワイルドストロベリー（Ｆｒａｇａｒｉａ　 ｖ ｅｓｃａ）、ホアハウンド（Ｍａｒｒｕｂｉｕｍ　ｖｕｌｇａｒｅ）、マーシュマロウ （ Ａｌｔｈａｅａ　ｏｆｆｉｃｉｎａｌｉｓ）、オオバコ（Ｐｌａｎｔａｇｏ　ａｓｉａｔｉｃａ）、レモンバーベナ（Ａｌｏｙｓｉａ　ｔｒｉｐｈｙｌｌａ）、ヤロウ（Ａｃｈｉｌｌｅａ　ｍｉｌｌｅｆｏｌｉｕｍ）、アイスランドモス（Ｃｅｔｒａｒｉａ　ｉｓｌａｎｄｉｃａ）、アマチャヅル（Ｈｙｄｒａｎｇｅ　ｓｅｒｒａｔａ）、およびフキ（Ｐｅｔａｓｉｔｅｓ　ｊａｐｏｎｉｃｕｓ）から選択される１種または２種以上の植物抽出物がインフルエンザウイルス不活化効果を示すことが特許文献１に記載されている。しかし、特許文献１で使用される植物抽出物は、水／エタノール（又は有機溶媒）を用いた抽出法で得られたものであり、食品に配合して経口投与することを意図している。 For example, raspberry (Rubus idaeus), strawberry (Fragaria vesca 、), blackberry (Rubus fruticosus), fig (Ficus carica), akaza (Cenopodium ａｔ ａｔ ａｔ ａｔ ｕ ｕ ｕ ｕ ｕ ｍ ｕ ｍ ｒｉ ｒｉ ｍ ア 、) , Apples (Malus pumila 、), violets (Viola odorata), kuromoji (Lindera umbellata), guarana (Paullinia cupana), Butteria ツ fusicinaris, tsuyuna (Communis) Zuna (Capsella bursapastoris), Enmeisou (Rabdosia japonica), Wild Strawberry (Fragaria v esca), Hoahaundo (Marrubium vulgare), Marsh mallow (Althaea officinalis), plantain (Plantago asiatica), lemon verbena (Aloysia triphylla), Yarrow (Achillea millefolium ), One or more plant extracts selected from Icelandic moss (Cetraria islandica), Amacula (Hydrangee serrata), and Butterfly (Petasites japonicus), inactivate influenza virus. To show results is described in Patent Document 1. However, the plant extract used in Patent Literature 1 is obtained by an extraction method using water / ethanol (or an organic solvent), and is intended to be orally administered after being added to a food.
　特許文献２には、ドクダミ（Ｈｏｕｔｔｕｙｎｉａ　ｃｏｒｄａｔａ　Ｔｈｕｎｂｏ）の水蒸気蒸留により得られる精油成分がインフルエンザウイルス、単純ヘルペスウイルス１型（ＨＳＶ－１）、エイズウイルス（ＨＩＶ）等に対して不活化効果を示すことが記載され、特許文献３には、パチョリ（Ｐｏｇｏｓｔｅｍｏｎ　ｃａｂｌｉｎ　Ｂｅｎｔｈ．）精油抽出物がインフルエンザウイルス不活化効果を有することが記載されている。しかし、特許文献２において有効成分として特定されているのは、精油成分に含まれるｎ－デシルアルデヒド、ｎ－ドデシルアルデヒド及びメチルｎ－ノニルケトンという非テルペン化合物であり、特許文献３における有効成分はパチョリをアルコール又はｎ－ヘキサンで抽出した後に分画して得られるパチョリアルコール（パチョール）であるとされている。 Patent Literature 2 discloses that an essential oil component obtained by steam distillation of Houttuynia {cordata} Thunbo has an inactivating effect on influenza virus, herpes simplex virus type 1 (HSV-1), AIDS virus (HIV) and the like. Patent Document 3 describes that an essential oil extract of patchouli (Pogostemon @ cablin @ Benth.) Has an influenza virus inactivating effect. However, non-terpene compounds such as n-decylaldehyde, n-dodecylaldehyde and methyl n-nonyl ketone contained in essential oil components are specified as active ingredients in Patent Document 2, and the active ingredient in Patent Document 3 is patchouli. Is extracted with alcohol or n-hexane, and then fractionated to obtain patchouli alcohol (patchol).
　特許文献４には、モミの葉の抽出物（モミ精油）が抗インフルエンザウイルス剤として有用であることが開示されているが、該精油中は、３０質量％以上のボルニルアセテートを含有するのが好ましく、それにカンフェン、ピネン、およびリモネンを加えた合計量がモミ精油の全量基準で９０質量％以上含有しているのが好ましいとされている。特許文献５には、ピネン類などのテルペン系誘導体、オイゲノールなどのフェノール類およびサンダルウッド油が麻疹ウイルス等の病原性有膜ウイルスに対し不活化効果を示すことが報告されている。 Patent Document 4 discloses that an extract of fir leaves (fir essential oil) is useful as an anti-influenza virus agent, but the essential oil contains at least 30% by mass of bornyl acetate. It is said that it is preferable that the total amount of added camphene, pinene and limonene be 90% by mass or more based on the total amount of the fir essential oil. Patent Document 5 reports that terpene derivatives such as pinenes, phenols such as eugenol, and sandalwood oil have an inactivating effect on pathogenic membrane viruses such as measles virus.
　しかしながら、精油に関しては、安全性（皮膚刺激性）の面で、ウイルス不活化効果量を含有させるのは現実的ではなく、そのため、より少量で効果を発揮する安全な天然成分を含有するウイルス不活化剤の開発が強く望まれていた。 However, for essential oils, it is not realistic to include an effective amount of virus inactivation in terms of safety (skin irritation). Therefore, virus essential oils containing safe natural ingredients that exert their effects in smaller amounts are not practical. The development of activators has been strongly desired.
　一方、天然成分ではないが、ジメチルオクタデシル［３－（トリエトキシシリル）プロピル］アンモニウムクロライド（ＥｔＡＣ）のようなケイ素を含有する第４級アンモニウムカチオンが、義歯洗浄剤などの口腔清浄剤などとして安全であり、インフルエンザウイルスやノロウイルスなどのウイルスを不活性化する能力を有することも報告されている（特許文献６）。しかし、特許文献６では、前記第４級アンモニウムカチオンの構造が僅かに相違するだけで、抗ウイルス効果や安定性に問題が生じ得ることが示唆されている（段落０００８及び０００９）。 On the other hand, although not a natural component, a quaternary ammonium cation containing silicon, such as dimethyloctadecyl [3- (triethoxysilyl) propyl] ammonium chloride (EtAC), is safe as a mouthwash such as a denture cleaner. It has also been reported that it has the ability to inactivate viruses such as influenza virus and norovirus (Patent Document 6). However, Patent Document 6 suggests that a slight difference in the structure of the quaternary ammonium cation may cause a problem in antiviral effect and stability (paragraphs 0008 and 0009).
特開２００４－５９４６３号公報JP-A-2004-59463 特開平７－１１８１６０号公報JP-A-7-118160 特開２０１１－７９８００号公報JP 2011-79800 A 特開２０１１－８４５０３号公報JP 2011-84503 A 特開平５－３０６２１７号公報JP-A-5-306217 特開２０１１－９８９７６号公報JP 2011-98976 A
　本発明は上記のような技術状況の下、細菌やウイルスのみならず、花粉やＰＭ２．５等の大気汚染物質といった皮膚に悪影響を与え得る刺激物質が増加している現状に鑑みてなされたものであり、皮膚刺激を生じない程度の量で効果を発揮するウイルス不活化剤、および該ウイルス不活化剤を含有する皮膚外用剤組成物を提供することを目的とする。 The present invention has been made in view of the current situation in which, in the above technical situation, not only bacteria and viruses but also stimulants that can adversely affect the skin, such as pollen and air pollutants such as PM2.5, are increasing. It is an object of the present invention to provide a virus inactivating agent exhibiting an effect in such an amount that does not cause skin irritation, and a skin external preparation composition containing the virus inactivating agent.
　本発明者らは、上記課題を解決するために鋭意検討した結果、特定の植物から抽出される精油の１種または２種以上、及び／又はカチオン化デンプンを有効成分として配合することにより、皮膚刺激を生じず安全に優れたウイルス不活化効果を示すことを見出し、本発明を完成するに至った。 The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, blending one or more of essential oils extracted from a specific plant and / or cationized starch as an active ingredient, The present inventors have found that the present invention exhibits a safe and excellent virus inactivating effect without irritation, thereby completing the present invention.
　すなわち、本発明は以下を包含する。
［１］有効成分として、ハッカ油、ユーカリ油、ローズマリー油、セージ油、ティーツリー油、月桃油、ペパーミント油、レモングラス油、カユプテ油、ニアウリ・シネオール油、ライム油、レモン油、レモンバーベナ油、セントジョーンズワート油、ラビンツァラ油、ローズウッド油、メリッサ/レモンバーム油、ミルラ油、マンダリン油、ベチバー油、フランキンセンス油、シトロネラ油、カルダモン油、アンジェリカ油、およびカチオン化デンプンから選ばれる１種または２種以上を含有することを特徴とするウイルス不活化剤。
［２］有効成分として、ハッカ油、ユーカリ油、ローズマリー油、およびセージ油からなる群から選択される１種または２種以上を含有することを特徴とする、上記［１］に記載のウイルス不活化剤。
［３］有効成分として、ハッカ油、ユーカリ油、ローズマリー油、およびセージ油からなる群から選択される３種を含有することを特徴とする、上記［２］に記載のウイルス不活化剤。
［４］有効成分として、ハッカ油、ユーカリ油、ローズマリー油、およびセージ油を含有することを特徴とする、上記［２］に記載のウイルス不活化剤。
［５］リモネン含有量が合計０．００６質量％以上である、上記［１］から［４］のいずれか一つに記載のウイルス不活化剤。
［６］有効成分として、カチオン化デンプンを含有することを特徴とする、上記［１］に記載のウイルス不活化剤。
［７］カチオン化デンプンが、下記式（Ｉ）：
Figure JPOXMLDOC01-appb-C000002
 ［式（Ｉ）中、Ｘ- は無機酸あるいは有機酸から誘導されるアニオンを示し；
ａ、ｂは、ａ＋ｂ＝１としたとき、ａは０．６～０．９、ｂは０．４～０．１であり；
平均分子量が３万～１００万である。］
で表されるカチオン性ポリマーである、上記［１］または［６］に記載のウイルス不活化剤。
［８］カチオン化デンプンの平均分子量が１０万～５０万である、上記［１］、［６］および［７］のいずれか一つに記載のウイルス不活化剤。
［９］カチオン化デンプンが塩化ヒドロキシプロピルトリモニウムデンプンである、上記［１］および［６］から［８］のいずれか一つに記載のウイルス不活化剤。
［１０］カチオン化デンプンの配合量が塩化ヒドロキシプロピルトリモニウムデンプンの純分換算で０．１質量％以上である、上記［１］および［６］から［９］のいずれか一つに記載のウイルス不活化剤。
［１１］ウイルスがエンベロープを有する一本鎖ＲＮＡウイルスである、上記［１］から［１０］のいずれか一つに記載のウイルス不活化剤。
［１２］エンベロープを有する一本鎖ＲＮＡウイルスがオルトミクソウイルス科に属するウイルスである、上記［１１］に記載のウイルス不活化剤。
［１３］オルトミクソウイルス科に属するウイルスがインフルエンザウイルスである、上記［１２］に記載のウイルス不活化剤。
［１４］上記［１］から［１３］のいずれか一つに記載のウイルス不活化剤を含むことを特徴とする皮膚外用剤組成物。
［１５］アルコールをさらに含有することを特徴とする、上記［１４］に記載の皮膚外用剤組成物。
［１６］アルコールの配合量が５０質量％以下である、上記［１５］に記載の皮膚外用剤組成物。 That is, the present invention includes the following.
[1] As active ingredients, mint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, cajeput oil, niau cineole oil, lime oil, lemon oil, lemon One or selected from verbena oil, St. John's wort oil, Rabinzala oil, rosewood oil, melissa / lemon balm oil, myrrh oil, mandarin oil, vetiver oil, frankincense oil, citronella oil, cardamom oil, angelica oil, and cationized starch. A virus inactivating agent comprising two or more types.
[2] The virus according to [1] above, wherein the virus contains one or more selected from the group consisting of peppermint oil, eucalyptus oil, rosemary oil, and sage oil as the active ingredient. Inactivator.
[3] The virus inactivating agent according to the above-mentioned [2], which contains three kinds of active ingredients selected from the group consisting of peppermint oil, eucalyptus oil, rosemary oil, and sage oil.
[4] The virus inactivating agent according to the above-mentioned [2], which contains mint oil, eucalyptus oil, rosemary oil, and sage oil as active ingredients.
[5] The virus inactivating agent according to any one of [1] to [4] above, wherein the total content of limonene is 0.006% by mass or more.
[6] The virus inactivating agent according to the above [1], which comprises a cationized starch as an active ingredient.
[7] The cationized starch is represented by the following formula (I):
Figure JPOXMLDOC01-appb-C000002
 [In the formula (I), X- represents an anion derived from an inorganic acid or an organic acid;
a and b are a = 0.6 to 0.9 and b is 0.4 to 0.1, where a + b = 1;
The average molecular weight is 30,000 to 1,000,000. ]
The virus inactivating agent according to the above [1] or [6], which is a cationic polymer represented by the following formula:
[8] The virus inactivating agent according to any one of the above [1], [6] and [7], wherein the cationized starch has an average molecular weight of 100,000 to 500,000.
[9] The virus inactivating agent according to any one of [1] and [6] to [8], wherein the cationized starch is hydroxypropyltrimonium chloride starch.
[10] The method according to any one of [1] and [6] to [9], wherein the amount of the cationized starch is 0.1% by mass or more in terms of pure content of hydroxypropyltrimonium chloride starch. Virus inactivator.
[11] The virus inactivating agent according to any one of [1] to [10], wherein the virus is a single-stranded RNA virus having an envelope.
[12] The virus inactivating agent according to [11], wherein the enveloped single-stranded RNA virus is a virus belonging to the orthomyxoviridae family.
[13] The virus inactivating agent according to the above [12], wherein the virus belonging to the orthomyxoviridae family is an influenza virus.
[14] A skin external preparation composition comprising the virus inactivating agent according to any one of [1] to [13].
[15] The skin external preparation composition according to the above [14], further comprising an alcohol.
[16] The composition for external use on skin according to the above [15], wherein the content of the alcohol is 50% by mass or less.
　本発明のウイルス不活化剤の一態様では、好ましくはリモネン含有量が少ない精油を複数組み合わせてリモネン合計量を所定量以上とすることにより、皮膚刺激を生じずに優れたウイルス不活化効果を示す。また、本発明のウイルス不活化剤は、カチオン化デンプンという天然由来の成分を配合することにより優れたウイルス不活化効果を示す。従って、本発明のウイルス不活化剤を含有する皮膚外用剤組成物は、安全かつ容易にウイルス不活作用を有するという利点がある。 In one embodiment of the virus inactivating agent of the present invention, preferably, by combining a plurality of essential oils having a low limonene content to make the total amount of limonene a predetermined amount or more, an excellent virus inactivating effect is produced without causing skin irritation. . Further, the virus inactivating agent of the present invention exhibits an excellent virus inactivating effect by blending a naturally derived component called cationized starch. Therefore, the skin external preparation composition containing the virus inactivating agent of the present invention has an advantage of having a virus inactivating effect safely and easily.
　以下、本発明についてさらに詳細に説明する。 Hereinafter, the present invention will be described in more detail.
　本発明のウイルス不活化剤の一態様は、１種または２種以上の植物抽出物を有効成分とするものであって、該植物抽出物が（シソ科ハッカ属）ハッカ、（フトモモ科ユーカリ属）ユーカリ、（シソ科マンネンロウ属）ローズマリー、（シソ科アキギリ属）セージ、（フトモモ科コバノブラシノキ属）ティーツリー、（ショウガ科ハナミョウガ属）月桃、（シソ科ハッカ属）ペパーミント、（イネ科オガルカヤ属）レモングラス、（フトモモ科コバノブラシノキ属）カユプテ、（フトモモ科メラレウカ属）ニアウリ・シネオール、（ミカン科ミカン属）ライム、（ミカン科ミカン属）レモン、（クマツヅラ科コウスイボク属）レモンバーベナ、（オトギリソウ科オトギリソウ属）セントジョーンズワート、（クスノキ科ニッケイ属）ラビンツァラ、（マメ科ツルサイチ属）ローズウッド、（シソ科コウスイハッカ属）メリッサ/レモンバーム、（カンラン科コンミフォラ属）ミルラ、（ミカン科ミカン属）マンダリン、（イネ科オキナワミチシバ属）ベチバー、（カンラン科ボスウェリア属）フランキンセンス、（イネ科オガルカヤ属）シトロネラ、（ショウガ科ショウズク属）カルダモン、および（セリ科シシウド属）アンジェリカからなる群から選択される植物由来のものであることを特徴としている。 One embodiment of the virus inactivating agent of the present invention comprises one or more plant extracts as an active ingredient, and the plant extracts are selected from the group consisting of mint (Lamiaceae, mint) and (Lumaria eucalyptus). ) Eucalyptus, (Lamiaceae Mannenlow) Rosemary, (Lamiaceae L. spp.) Sage, (Lamiaceae L. spp.) Tea Tree, (Zingiberaceae Hanamyoga) L. peach, (Lamiaceae mint) Peppermint, (Rice) Family Ogarukaya) Lemongrass, Leafgrass (Dipterocarpaceae) Kayupute, (Diptera: Melaleuca) Niauli cineole, (Rutaceae Rutaceae) lime, (Rutaceae Rutaceae) lemon, (Lepidoptera: Rubiaceae) Lemon Verbena, (Hypericum perforatum) St. John's wort, (Camphoraceae Nikkei) Labins La, (Fabaceae, Crassaceae) Rosewood, (Lamiaceae, Laminariaceae) Melissa / Lemon balm, (Orchidaceae, Commiphora) Myrrh, (Rutaceae, Citrus) Mandarin, (Poaceae, Oleraceae) Vetiver, (Kanran) The plant is characterized by being derived from a plant selected from the group consisting of the family Boswellia frankincense, (Poaceae Ogarkaya) Citronella, (Zingiberaceae Zygium) cardamom, and (Ceramiaceae Sisudo) genus Angelica.
　本発明における植物抽出物としては、前記の植物中に含まれる芳香物質として抽出した「精油」が好ましい。
　本発明における「精油（エッセンシャルオイル）」は、上記の植物またはその乾燥物から水蒸気蒸留によって得られる狭義の精油が好ましく用いられるが、それに限定されない。例えば、抽出法や圧搾法等の他の方法で植物から抽出された油分も、精油成分（芳香物質等）を含むものである限り、本発明における「精油」に包含される。 As the plant extract in the present invention, “essential oil” extracted as an aromatic substance contained in the above-mentioned plant is preferable.
As the “essential oil” (essential oil) in the present invention, an essential oil in a narrow sense obtained by steam distillation from the above-mentioned plant or a dried product thereof is preferably used, but is not limited thereto. For example, an oil component extracted from a plant by another method such as an extraction method or a squeezing method is also included in the “essential oil” in the present invention as long as it contains an essential oil component (such as an aromatic substance).
　植物から精油を抽出する他の方法としては、例えば溶剤抽出法（アルコール抽出法、有機溶剤抽出法など）、油脂吸着抽出法（温浸法または冷浸法）、超臨界流体抽出法等が知られている。植物の精油含量が少ない等の理由により水蒸気蒸留が適用できないときには溶媒抽出法が用いられることが多い。抽出に用いる溶媒としては、限定するものではないが、例えばエタノール、メタノール、プロパノール、イソプロパノール、ブタノールなどのアルコール類、アセトンなどの比較的高極性のものからヘキサンなどの低極性のものを含む有機溶媒が例示される。これらの精油抽出方法の詳細については、「特許庁広報 周知慣用技術集（香料）第Ｉ部　香料一般」（平成１１（１９９９）年１月２９日、日本国特許庁発行、ｐｐ．４－２１（２・１・１　植物性香料））等の文献を参照することができる。 Other methods for extracting essential oils from plants include, for example, a solvent extraction method (alcohol extraction method, organic solvent extraction method, etc.), an oil / fat adsorption extraction method (digestion method or cold immersion method), and a supercritical fluid extraction method. Have been. When steam distillation cannot be applied, for example, because the essential oil content of the plant is low, a solvent extraction method is often used. Solvents used for the extraction are not limited, but include, for example, alcohols such as ethanol, methanol, propanol, isopropanol, and butanol, and organic solvents including relatively high-polarity solvents such as acetone to low-polarity solvents such as hexane. Is exemplified. For details of these essential oil extraction methods, see "Public Office of Public Relations, Well-known Conventional Techniques (Fragrances), Part I, General Perfume" (published by the Japan Patent Office, January 29, 1999, pp. 4-21). References such as (2.1.1 {vegetable flavor)) can be referred to.
　本発明における「精油」は、上記の方法で得た油分を、例えば多孔性ビーズ、シリカゲルやアルミナなどの担体を用いた疎水性または吸着クロマトグラフィー等の各種精製手法を用いて更に精製・濃縮したものであってもよい。 The "essential oil" in the present invention is obtained by further purifying and concentrating the oil obtained by the above method using various purification techniques such as hydrophobic beads or adsorption chromatography using a carrier such as porous beads, silica gel or alumina. It may be something.
　本明細書では、段落００１５に列挙した各植物から得られた「精油」を、各々、ハッカ油、ユーカリ油、ローズマリー油、セージ油、ティーツリー油、月桃油、ペパーミント油、レモングラス油、カユプテ油、ニアウリ・シネオール油、ライム油、レモン油、レモンバーベナ油、セントジョーンズワート油、ラビンツァラ油、ローズウッド油、メリッサ/レモンバーム油、ミルラ油、マンダリン油、ベチバー油、フランキンセンス油、シトロネラ油、カルダモン油、およびアンジェリカ油と称する。 As used herein, "essential oil" obtained from each of the plants listed in paragraph 0015 is referred to as peppermint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, respectively. , Kajupte oil, Niauli Cineol oil, Lime oil, Lemon oil, Lemon verbena oil, St. John's wort oil, Rabinzala oil, Rosewood oil, Melissa / Lemon balm oil, Myrrh oil, Mandarin oil, Vetiver oil, Frankincense oil, Citronella oil, Called cardamom oil and angelica oil.
　本発明のウイルス不活化剤は、ハッカ油、ユーカリ油、ローズマリー油、セージ油、ティーツリー油、月桃油、ペパーミント油、レモングラス油、カユプテ油、ニアウリ・シネオール油、ライム油、レモン油、レモンバーベナ油、セントジョーンズワート油、ラビンツァラ油、ローズウッド油、メリッサ/レモンバーム油、ミルラ油、マンダリン油、ベチバー油、フランキンセンス油、シトロネラ油、カルダモン油、およびアンジェリカ油からなる群から選択される精油の１種または２種以上を有効成分として含有する。好ましくは２種、より好ましくは３種、更に好ましくは４種またはそれ以上の精油を含有するのが好ましい。 The virus inactivating agent of the present invention includes peppermint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, cajeput oil, niau cineole oil, lime oil, and lemon oil. Essential oil selected from the group consisting of, lemon verbena oil, St. John's wort oil, Rabinzala oil, rosewood oil, melissa / lemon balm oil, myrrh oil, mandarin oil, vetiver oil, frankincense oil, citronella oil, cardamom oil, and angelica oil As active ingredients. Preferably, it contains two, more preferably three, even more preferably four or more essential oils.
　前記の精油の中でも、リモネンの含有量が精油１００ｇ当たり１０ｇ以下、好ましくは８ｇ以下、より好ましくは６ｇ以下の精油を選択するのが好ましい。特に、ハッカ油、ユーカリ油、ローズマリー油、およびセージ油からなる群から選択される少なくとも１種を用いるのが好ましい。本発明のウイルス不活化剤の好ましい態様は、ハッカ油、ユーカリ油、ローズマリー油、およびセージ油からなる群から選択される２種、好ましくは３種、より好ましくは４種を有効成分として含有する。 中 で も Among the above essential oils, it is preferable to select an essential oil having a limonene content of 10 g or less, preferably 8 g or less, more preferably 6 g or less per 100 g of the essential oil. In particular, it is preferable to use at least one selected from the group consisting of mint oil, eucalyptus oil, rosemary oil, and sage oil. A preferred embodiment of the virus inactivating agent of the present invention comprises two, preferably three, and more preferably four as active ingredients selected from the group consisting of peppermint oil, eucalyptus oil, rosemary oil, and sage oil. I do.
　なお、本発明のウイルス不活化剤は、配合する精油に含まれるリモネンの含有量が、ウイルス不活化剤の全量に対して０．００６質量％以上となるように精油を組み合わせて配合するのが好ましい。リモネンの配合量が０．００６質量％未満であると十分なウイルス不活化効果が得られない。 The virus inactivating agent of the present invention is preferably combined with the essential oil so that the content of limonene contained in the essential oil to be blended is 0.006% by mass or more based on the total amount of the virus inactivating agent. preferable. If the amount of limonene is less than 0.006% by mass, a sufficient virus inactivating effect cannot be obtained.
　リモネンは、主に柑橘類の果皮に含まれる単環式モノテルペン炭化水素である。リモネンは、オレンジやレモン等の柑橘類から得られる精油の主成分をなすが、橙皮油やレモン油に含まれるリモネンはＤ体であり、ハッカ油等に含まれるリモネンはＬ体であることが知られている。本発明で用いられるリモネンはＤ体、Ｌ体又はＤ体とＬ体の混合物（ラセミ体等）であってよく、特に限定されない。すなわち、本発明のウイルス不活剤は、Ｄ－リモネンを０．００６質量％以上含有する態様、Ｌ－リモネンを０．００６質量％以上含有する態様、及びＤ－リモネンとＬ－リモネンを合計で０．００６質量％以上含有する態様を含む。 Perimonene is a monocyclic monoterpene hydrocarbon mainly contained in the citrus peel. Limonene is a main component of essential oils obtained from citrus fruits such as oranges and lemons, but limonene contained in orange peel oil and lemon oil is D-form, and limonene contained in peppermint oil and the like is L-form. Are known. The limonene used in the present invention may be a D-form, an L-form or a mixture of a D-form and an L-form (a racemic body or the like), and is not particularly limited. That is, the virus inactivator of the present invention has an embodiment containing D-limonene of 0.006% by mass or more, an embodiment containing L-limonene of 0.006% by mass or more, and a total of D-limonene and L-limonene. The embodiment containing 0.006% by mass or more is included.
　リモネン配合量の上限は特に限られないが、通常は、０．０５質量％以下、好ましくは０．０４質量％以下、０．０３質量％以下、あるいは０．０２質量％以下である。リモネンの配合量が多くなり過ぎると皮膚刺激性を生じる可能性がある。
　なお、配合する精油の全量に対するリモネン量は、精油１００ｇに対して５ｇ未満、好ましくは４．５ｇ未満とするのが好ましい。 The upper limit of the amount of limonene is not particularly limited, but is usually 0.05% by mass or less, preferably 0.04% by mass or less, 0.03% by mass or less, or 0.02% by mass or less. Excessive amounts of limonene may cause skin irritation.
The amount of limonene relative to the total amount of essential oil to be blended is preferably less than 5 g, preferably less than 4.5 g, per 100 g of essential oil.
　本発明のウイルス不活化剤の別の態様は、カチオン化デンプンを有効成分とするものである。
　カチオン化デンプンは、複数のグルコースがα－１，４－グルコシド結合を介して結合した構造を基本骨格とするデンプンに、第４級アンモニウム等のカチオン性基を導入したカチオン性ポリマーである。 Another embodiment of the virus inactivator of the present invention comprises a cationized starch as an active ingredient.
Cationized starch is a cationic polymer obtained by introducing a cationic group such as quaternary ammonium into starch having a basic skeleton of a structure in which a plurality of glucoses are bonded via α-1,4-glucosidic bonds.
　本発明で用いられるカチオン化デンプンとしては、下記式（Ｉ）：
Figure JPOXMLDOC01-appb-C000003
 で表されるカチオン性ポリマーが好ましい。 The cationized starch used in the present invention includes the following formula (I):
Figure JPOXMLDOC01-appb-C000003
 The cationic polymer represented by is preferred.
　上記式（Ｉ）中の各記号は以下の意味を表す。
　Ｘ- は、無機酸あるいは有機酸から誘導されるアニオンを示す。無機酸としては、塩酸、硫酸、硝酸などが例示され、有機酸としては、酢酸等のカルボン酸が例示される。上記式（Ｉ）におけるアニオンＸ－としては、ハロゲン化物イオン、特にＣｌ－が好ましい。
　ａ及びｂは、ポリマー中の各モノマー数及び各モノマーの比率を表す。各モノマー数を表す場合、式（Ｉ）で示すカチオン化デンプンの平均分子量（重量平均分子量：Ｍｗ）は３万～１００万が好ましく、より好ましくは１０万～５０万であるので、ａ及びｂは、平均分子量が前記の範囲内となるような値をとる。各モノマーの比率を表す場合は、例えば、ａ＋ｂ＝１と仮定すると、ａは０．６～０．９、好ましくは０．７～０．８、より好ましくは約０．７５であり、ｂは、０．４～０．１、好ましくは０．３～０．２、より好ましくは約０．２５である。 Each symbol in the above formula (I) has the following meaning.
X - is an anion derived from inorganic or organic acids. Examples of the inorganic acid include hydrochloric acid, sulfuric acid, and nitric acid, and examples of the organic acid include carboxylic acid such as acetic acid. The anion X − in the above formula (I) is preferably a halide ion, particularly Cl − .
a and b represent the number of each monomer in the polymer and the ratio of each monomer. When the number of each monomer is represented, the average molecular weight (weight average molecular weight: Mw) of the cationized starch represented by the formula (I) is preferably 30,000 to 1,000,000, and more preferably 100,000 to 500,000. Takes a value such that the average molecular weight falls within the above range. When expressing the ratio of each monomer, for example, assuming that a + b = 1, a is 0.6 to 0.9, preferably 0.7 to 0.8, more preferably about 0.75, and b is , 0.4-0.1, preferably 0.3-0.2, more preferably about 0.25.
　式（Ｉ）で表されるカチオン化デンプンは、化粧品成分表示名称で「塩化ヒドロキシプロピルトリモニウムデンプン」である。当該表示名称で市販されている商品として、例えば、「センサマーＣＩ－５０」（ＮＡＬＣＯ　Ｐｅｒｆｏｒｍａｎｃｅ　Ｐｒｏｄｕｃｔｓ社製）、「ＤＯＣＣＴＡＲＣＨ　ＣＰ」（ＤＯＣ　Ｊａｐａｎ社製）、「アミロマー２５Ｌ」（Ｇｒａｅｆｅ　Ｃｈｅｍｉｅ社製）、「アミロマー５０Ｍ」（Ｇｒａｅｆｅ　Ｃｈｅｍｉｅ社製）、「ファーマルＭＳ５９４０」（Ｃｏｒｎ　Ｐｒｏｄｕｃｔｓ　Ｉｎｔｅｒｎａｔｉｏｎａｌ社製）、「エキセルＦＭ－００４」（日本澱粉社製）等が例示でき、これら市販品を用いることができる。これらの中でも、「センサマーＣＩ－５０」（平均分子量＝２０万；ａ：ｂ＝０．７５：０．２５）が好ましく使用できる。 カ チ オ ン The cationized starch represented by the formula (I) is “hydroxypropyltrimonium chloride starch” under the cosmetic ingredient designation. Commercially available products under the display name include, for example, “Sensormer CI-50” (manufactured by NALCO Performance Products), “DOCCARCHCH CP” (manufactured by DOC Japan), “Amilomer 25L” (manufactured by Graef Chemie), “ "Amilomer 50M" (manufactured by Graefe Chemie), "Famar MS5940" (manufactured by Corn Products International), "Exel FM-004" (manufactured by Nippon Starch Co., Ltd.) and the like can be used, and these commercially available products can be used. Among these, “Sensormer CI-50” (average molecular weight = 200,000; a: b = 0.75: 0.25) can be preferably used.
　カチオン化デンプンは、カチオン化セルロースやポリクオタニウム等とともにカチオン性ポリマーとして主にヘアコンディショニング剤として使用されているが、カチオン化デンプンがウイルス不活化効果を有することは、本発明によって初めて見出された驚くべき知見である。 Cationized starch is mainly used as a hair conditioning agent as a cationic polymer together with cationized cellulose, polyquaternium and the like, but it has been surprisingly discovered by the present invention that cationized starch has a virus inactivating effect for the first time. It is an important finding.
　本発明のウイルス不活化剤におけるカチオン化デンプンの配合量は、ウイルス不活化剤の全量に対して、ポリマー純分で０．１質量％以上、好ましくは０．１５質量％以上、より好ましくは０．２質量％以上である。配合量が０．１質量％未満であると十分なウイルス不活化効果が得られない。カチオン化デンプンの配合量上限は、特に限定されないが、通常は５質量％以下、好ましくは３質量％以下、より好ましくは２質量％以下である。 The amount of the cationized starch in the virus inactivating agent of the present invention is 0.1% by mass or more, preferably 0.15% by mass or more, more preferably 0% by mass or more, based on the total amount of the virus inactivating agent. 0.2 mass% or more. If the amount is less than 0.1% by mass, a sufficient virus inactivating effect cannot be obtained. The upper limit of the amount of the cationized starch is not particularly limited, but is usually 5% by mass or less, preferably 3% by mass or less, more preferably 2% by mass or less.
　本発明および本願明細書において、「ウイルス不活化」とは、ウイルスの感染または増殖能力を除去もしくは著しく低下させることを意味する。本発明のウイルス不活化剤で不活化できるウイルスについては特に限定はなく、ゲノムの種類、エンベロープの有無等に拘わらず、様々なウイルスを不活化対象とすることができる。 に お い て In the present invention and in the present specification, “virus inactivation” means removing or significantly reducing the ability of a virus to infect or proliferate. The virus that can be inactivated by the virus inactivating agent of the present invention is not particularly limited, and various viruses can be inactivated regardless of the type of genome, the presence or absence of an envelope, and the like.
　例えば、Ａ型、Ｂ型、Ｃ型インフルエンザウイルス、イサウイルス、クアランジャウイルス、トゴトウイルス、ライノウイルス、ポリオウイルス、ロタウイルス、ノロウイルス、エンテロウイルス、ヘパトウイルス、アストロウイルス、サポウイルス、Ｅ型肝炎ウイルス、パラインフルエンザウイルス、ムンプスウイルス、麻疹ウイルス、ヒトメタニューモウイルス、ＲＳウイルス、ニパウイルス、ヘンドラウイルス、黄熱ウイルス、デングウイルス、日本脳炎ウイルス、ウエストナイルウイルス、Ｂ型、Ｃ型肝炎ウイルス、東部および西部馬脳炎ウイルス、風疹ウイルス、ラッサウイルス、フニンウイルス、マチュポウイルス、グアナリトウイルス、サビアウイルス、クリミアコンゴ出血熱ウイルス、ハンタウイルス、シンノンブレウイルス、狂犬病ウイルス、エボラウイルス、マーブルグウイルス、コウモリリッサウイルス、ヒトＴ細胞白血病ウイルス、ヒト免疫不全ウイルス、ヒトコロナウイルス、ＳＡＲＳコロナウイルス、ヒトポルボウイルス、ポリオーマウイルス、ヒトパピローマウイルス、アデノウイルス、ヘルペスウイルス、水痘、帯状発疹ウイルス、ＥＢウイルス、サイトメガロウイルス、天然痘ウイルス、サル痘ウイルス、牛痘ウイルス、モラシポックスウイルス、パラポックスウイルスなどを挙げることができ、好ましくはエンベロープを有する一本鎖ＲＮＡウイルス、より好ましくはオルトミクソウイルス科に属する、Ａ型、Ｂ型、Ｃ型インフルエンザウイルス、イサウイルス、クアランジャウイルス、およびトゴトウイルス、特に好ましくはインフルエンザウイルスを不活化対象とすることができる。 For example, influenza A, B, influenza C, isavirus, quaranja virus, togotovirus, rhinovirus, poliovirus, rotavirus, norovirus, enterovirus, hepatovirus, astrovirus, sapovirus, hepatitis E virus, Parainfluenza virus, mumps virus, measles virus, human metapneumovirus, respiratory syncytial virus, nipavirus, Hendra virus, yellow fever virus, dengue virus, Japanese encephalitis virus, West Nile virus, type B, hepatitis C virus, eastern and western horses Encephalitis virus, rubella virus, Lassa virus, Junin virus, Machupo virus, Guanarito virus, Savior virus, Crimean Congo hemorrhagic fever virus, Hanta virus, Shinnonbrewi Virus, rabies virus, Ebola virus, Marburg virus, bat lyssa virus, human T cell leukemia virus, human immunodeficiency virus, human coronavirus, SARS coronavirus, human porvovirus, polyoma virus, human papillomavirus, adenovirus, herpes Virus, varicella, shingles virus, EB virus, cytomegalovirus, smallpox virus, monkeypox virus, cowpox virus, morasipox virus, parapoxvirus, etc., and preferably single-stranded RNA having an envelope Viruses, more preferably belong to the family Orthomyxoviridae, type A, type B, type C influenza viruses, isaviruses, quaranjaviruses and togotoviruses, particularly preferably influenzae A The virus can be inactivated target.
　本発明のウイルス不活化剤は、ハッカ油、ユーカリ油、ローズマリー油、セージ油、ティーツリー油、月桃油、ペパーミント油、レモングラス油、カユプテ油、ニアウリ・シネオール油、ライム油、レモン油、レモンバーベナ油、セントジョーンズワート油、ラビンツァラ油、ローズウッド油、メリッサ/レモンバーム油、ミルラ油、マンダリン油、ベチバー油、フランキンセンス油、シトロネラ油、カルダモン油、およびアンジェリカ油からなる群から選択される精油の１種または２種以上、あるいは、カチオン化デンプンを、各々単独で配合することで十分な効果を奏するが、精油とカチオン化デンプンとを組み合わせて有効成分としたウイルス不活化剤としてもよい。 The virus inactivating agent of the present invention includes peppermint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, cajeput oil, niau cineole oil, lime oil, and lemon oil. Essential oil selected from the group consisting of, lemon verbena oil, St. John's wort oil, Rabinzala oil, rosewood oil, melissa / lemon balm oil, myrrh oil, mandarin oil, vetiver oil, frankincense oil, citronella oil, cardamom oil, and angelica oil A sufficient effect can be obtained by blending one or more of the above, or a cationized starch alone, but a virus inactivating agent may be used as an active ingredient by combining an essential oil and a cationized starch.
　本発明は、上記のウイルス不活化剤を含有する皮膚外用剤組成物を提供する。本発明の「皮膚外用剤組成物」は、皮膚（頭皮を含む）に適用される外用剤組成物であればよく、例えば化粧料（基礎化粧料およびメークアップ化粧料を含む）、洗浄料、外用医薬品、および外用医薬部外品等を含むことができる。
　本発明の皮膚外用剤組成物は、上記したウイルス不活化剤のみからなる形態でもよく、一般的に皮膚外用剤組成物に用いられる各種成分を必要に応じて適宜配合した形態でもよい。 The present invention provides a skin external preparation composition containing the above virus inactivating agent. The "skin external preparation composition" of the present invention may be any external preparation composition applied to the skin (including the scalp), and includes, for example, cosmetics (including basic cosmetics and makeup cosmetics), cleaning agents, It can include external medicines, quasi-drugs, and the like.
The skin external preparation composition of the present invention may be in the form of the above-described virus inactivating agent alone, or may be in a form in which various components generally used in the skin external preparation composition are appropriately blended as necessary.
　例えば、本発明の皮膚外用剤組成物は、エタノール等の低級アルコール（炭素数６以下のアルコール）を含んでもよい。エタノール等の低級アルコールは、インフルエンザウイルスをはじめとする様々なウイルスに対する不活化効果を持つことが知られ、アルコールを高配合したウイルス不活化剤組成物も知られている。しかしながら、本発明の皮膚外用剤組成物においては、アルコールを配合する場合の配合量を５０質量％以下、好ましくは４０％質量以下あるいは３０質量％以下とするのが好ましく、そのようにすることによって敏感肌の方も安心して使用することができる。 For example, the skin external preparation composition of the present invention may contain a lower alcohol such as ethanol (an alcohol having 6 or less carbon atoms). It is known that lower alcohols such as ethanol have an inactivating effect on various viruses including influenza virus, and a virus inactivating agent composition containing a high amount of alcohol is also known. However, in the skin external preparation composition of the present invention, the blending amount when the alcohol is blended is preferably 50% by mass or less, preferably 40% by mass or less, or 30% by mass or less. Sensitive skin can also be used with confidence.
　本発明の皮膚外用剤組成物に配合可能な他の任意成分としては、例えば、油分（動植物油、鉱物油、エステル油、ワックス油、シリコーン油、高級アルコール、リン脂質類、脂肪酸類等）、界面活性剤（アニオン性、カチオン性、両性または非イオン性界面活性剤）、ビタミン類（ビタミンＡ群、ビタミンＢ群、葉酸類、ニコチン酸類、パントテン酸類、ビオチン類、ビタミンＣ群、ビタミンＤ群、ビタミンＥ群、その他フェルラ酸、γ－オリザノール等）、紫外線吸収剤（ｐ－アミノ安息香酸、アントラニル、サリチル酸、クマリン、ベンゾトリアゾール、テトラゾール、イミダゾリン、ピリミジン、ジオキサン、フラン、ピロン、カンファー、核酸、アラントインおよびそれらの誘導体、アミノ酸系化合物、シコニン、バイカリン、バイカレイン、ベルベリン等）、抗酸化剤（ステアリン酸エステル、ノルジヒドログアセレテン酸、ジブチルヒドロキシトルエン、ブチルヒドロキシアニソール、パラヒドロキシアニソール、没食子酸プロピル、セサモール、セサモリン、ゴシポール等）、増粘剤（ヒドキシエチルセルロース、エチルセルロース、カルボキシエチルセルロース、メチルセルロース、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、ヒドキシプロピルセルロース、ニトロセルロース、ポリビニルアルコール、ポリビニルメチルエーテル、ポリビニルピロリドン、ポリビニルメタアクリレート、ポリアクリル酸塩 、カルボキシビニルポリマー、アラビアゴム、トラガントゴム、寒天、カゼイン、デキストリン、ゼラチン、ペクチン、アルギン酸およびその塩等）、保湿剤（プロピレングリコール、１，３－ブチレングリコール、ポリエチレングリコール、グリセリン、１ ，２－ペンタンジオール、ヘキシレングリコール、コンドロイチン硫酸およびその塩、ヒアルロン酸およびその塩、乳酸ナトリウム等）、水溶性高分子、ｐＨ調整剤、防腐・防黴剤、着色料、清涼剤、安定化剤、微生物培養代謝成分、血流促進剤、消炎剤、抗炎症剤、抗アレルギー剤、アミノ酸およびその塩、角質溶解剤、収斂剤、創傷治療剤、消臭・脱臭剤、各種粉末成分などが挙げられる。これらは１種を選択して配合してもよいし２種以上を併用してもよい。 Other optional components that can be added to the skin external preparation composition of the present invention include, for example, oils (animal and vegetable oils, mineral oils, ester oils, wax oils, silicone oils, higher alcohols, phospholipids, fatty acids, etc.), Surfactants (anionic, cationic, amphoteric or nonionic surfactants), vitamins (vitamin A group, vitamin B group, folic acid, nicotinic acid, pantothenic acid, biotin, vitamin C group, vitamin D group , Vitamin E group, other ferulic acid, γ-oryzanol, etc.), ultraviolet absorbers (p-aminobenzoic acid, anthranil, salicylic acid, coumarin, benzotriazole, tetrazole, imidazoline, pyrimidine, dioxane, furan, pyrone, camphor, nucleic acid, Allantoin and their derivatives, amino acid compounds, shikonin, baicalin, ba Kalein, berberine, etc.), antioxidants (such as stearic acid ester, nordihydroguaselethenoic acid, dibutylhydroxytoluene, butylhydroxyanisole, parahydroxyanisole, propyl gallate, sesamol, sesamolin, gossypol, etc.), and thickeners (hydr) Xyethylcellulose, ethylcellulose, carboxyethylcellulose, methylcellulose, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxypropylcellulose, nitrocellulose, polyvinyl alcohol, polyvinylmethylether, polyvinylpyrrolidone, polyvinylmethacrylate, polyacrylate, carboxyvinyl polymer, gum arabic , Tragacanth, agar, casein, dextrin, gelatin, pectin, algi Acids and salts thereof), humectants (propylene glycol, 1,3-butylene glycol, polyethylene glycol, glycerin, 1, 2-pentanediol, hexylene glycol, chondroitin sulfate and salts thereof, hyaluronic acid and salts thereof, sodium lactate Etc.), water-soluble polymers, pH adjusters, preservatives / antifungal agents, coloring agents, cooling agents, stabilizers, microbial culture metabolic components, blood flow promoters, anti-inflammatory agents, anti-inflammatory agents, anti-allergic agents, amino acids And salts thereof, keratolytic agents, astringents, wound healing agents, deodorants / deodorants, and various powder components. One of these may be selected and blended, or two or more thereof may be used in combination.
　本発明の皮膚外用剤組成物の剤型は任意であり、例えば、化粧水、クリーム、軟膏、乳液、ファンデーション、オイル、パック、石鹸（薬用石鹸も含む）、ボディソープ、口紅、香水、洗顔料、防臭剤（腋臭、足臭等）、浴用剤、シャンプー、コンディショナー、ヘアトニック、ヘアスプレー等の剤型とすることができる。 The dosage form of the skin external preparation composition of the present invention is arbitrary, and examples thereof include lotions, creams, ointments, emulsions, foundations, oils, packs, soaps (including medicated soaps), body soaps, lipsticks, perfumes, and facial cleansers. , Deodorant (armpit odor, foot odor, etc.), bath agent, shampoo, conditioner, hair tonic, hair spray and the like.
　本発明の皮膚外用剤組成物の形態は、その剤型に応じて、溶液状、クリーム状、ペースト状、ゲル状、ジェル状、泡状、固形状または粉末状とすることができる。
　本発明の皮膚外用剤組成物は、上述したウイルス不活化剤を必須成分として、剤型及び形態に応じた通常の方法に準じて調製可能である。 The form of the skin external preparation composition of the present invention can be in the form of a solution, cream, paste, gel, gel, foam, solid, or powder, depending on the dosage form.
The skin external preparation composition of the present invention can be prepared by using the above-described virus inactivating agent as an essential component according to a usual method depending on the dosage form and form.
　以下、実施例を挙げて本発明をさらに詳しく説明するが、本発明はこれらによって限定されるものではない。また実施例における「％」は、特に断らない限り、「質量％」を意味する。 Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto. In the examples, “%” means “% by mass” unless otherwise specified.
（実施例１）
インフルエンザウイルスに対する不活化効果（その１）
１）検体（試験液）の調製
　以下の表１に示す処方で、ウイルス不活化剤の検体（試験液）を調製した。 (Example 1)
Inactivating effect on influenza virus (1)
1) Preparation of Sample (Test Solution) A sample (test solution) of a virus inactivating agent was prepared according to the formulation shown in Table 1 below.
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
２）試験方法
　インフルエンザウイルスＡ型（Ｈ１Ｎ１／ＰＲ／８／３４）株を試験ウイルス株として用いた。
　表１に示した各検体（試験液）１．０８０ｍＬにウイルス液０．１２ｍＬ（１×１０4 ｐｆｕ／ｍＬ）を加え、３０分間反応後、ＳＣＤＬＰ培地で１０倍ずつ段階希釈し、あらかじめ９６穴プレートで培養していたイヌ腎臓細胞（ＭＤＣＫ）に接種し、３７℃、５％ＣＯ2 条件下で培養後、形成されたプラーク数を測定し、残存ウイルス感染力価を決定した。 2) Test method Influenza virus type A (H1N1 / PR / 8/34) strain was used as a test virus strain.
0.12 mL (1 × 10 4 pfu / mL) of the virus solution was added to 1.080 mL of each sample (test solution) shown in Table 1, and after reacting for 30 minutes, serially diluted 10-fold with SCDLP medium, and 96 wells were previously prepared. Canine kidney cells (MDCK) cultured on the plate were inoculated, cultured at 37 ° C. under 5% CO 2 , the number of plaques formed was measured, and the residual virus infectious titer was determined.
３）試験結果
　結果を表２に示した。下記の表２から明らかなように、ハッカ系精油４種（ハッカ油、ローズマリー油、ユーカリ油、セージ油）の組み合わせ（検体２）では、ウイルス感染力価の対数減少値が約４となり、インフルエンザウイルスに対して高い不活化効果を有することが示された。これに対して、精油の種類を減らす、あるいは精油の配合量を減らすことにより、リモネン量を０．００６質量％未満とした他の検体（３～８）では、いずれの場合にもウイルス不活化効果は認められなかった。 3) Test results The results are shown in Table 2. As is evident from Table 2 below, in the combination of four mint essential oils (mint oil, rosemary oil, eucalyptus oil, sage oil) (sample 2), the log reduction value of the virus infection titer was about 4, It was shown to have a high inactivating effect on influenza virus. On the other hand, in the other samples (3 to 8) in which the amount of limonene was less than 0.006% by mass by reducing the type of essential oil or the amount of the essential oil, the virus inactivation was in each case. No effect was observed.
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
（実施例２）
インフルエンザウイルスに対する不活化効果（その２）
１）検体（試験液）の調製
　以下の表３に示す処方で、ウイルス不活化剤の検体（試験液）を調製した。 (Example 2)
Inactivation effect on influenza virus (part 2)
1) Preparation of Sample (Test Solution) A sample (test solution) of a virus inactivating agent was prepared according to the formulation shown in Table 3 below.
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
２）試験方法
　上記実施例１に記載の試験方法に準ずる。 2) Test method According to the test method described in Example 1 above.
３）試験結果
　結果を表４に示した。下記表４から明らかなように、カチオン化デンプン（塩化ヒドロキシプロピルトリモニウムデンプン）をポリマー純分で０．２４質量％含有する検体１０は、ウイルス感染力価の対数減少値が４以上であり、非常に高いインフルエンザウイルス不活化効果を有することが認められた。これに対して、ポリマー純分で同程度の量（０．１質量％）のカチオン化セルロース誘導体（ヒドロキシエチルセルロースヒドロキシプロピルトリモニウムクロリド）を配合した検体１２、及び、有効量より少量（０．０２４質量％）のカチオン化デンプンを配合した検体１１では、ウイルス不活化効果は認められなかった。 3) Test results The results are shown in Table 4. As is clear from Table 4 below, the specimen 10 containing 0.24% by mass of the cationized starch (hydroxypropyltrimonium chloride starch) in a polymer pure content has a log reduction value of the virus infectious titer of 4 or more, It was found to have a very high influenza virus inactivation effect. On the other hand, the specimen 12 containing the same amount (0.1% by mass) of the cationized cellulose derivative (hydroxyethylcellulose hydroxypropyltrimonium chloride) in the pure polymer content, and a smaller amount than the effective amount (0.024%). (% By mass) in Sample 11, in which the cationized starch was blended, no virus inactivating effect was observed.
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000007
　以下に、本発明に係る皮膚外用剤組成物の他の処方例を挙げる。
（処方例１）皮膚外用剤（ウイルスブロックミスト）
配合成分　　　　　　　　　　　　　　　　　　　　　　　質量％
エタノール　　　　　　　　　　　　　　　　　　　　　　２０．０
カチオン化デンプン（＊）　　　　　　　　　　　　　　　１．０
クエン酸　　　　　　　　　　　　　　　　　　　　　　　０．０２
クエン酸ナトリウム　　　　　　　　　　　　　　　　　　０．０８
水　　　　　　　　　　　　　　　　　　　　　　　　　　残余
合計　　　　　　　　　　　　　　　　　　　　　　　　　１００
（＊）センサマーＣＩ－５０ Hereinafter, other formulation examples of the skin external preparation composition according to the present invention will be described.
(Prescription Example 1) Skin external preparation (virus block mist)
Ingredient mass%
Ethanol 20.0
Cationized starch (*) 1.0
Citric acid 0.02
Sodium citrate 0.08
Water Total 100
(*) Sensormer CI-50
　前記の処方例１の皮膚外用剤をミスト状ディスペンサーにて吐出することで、抗ウイルスミストが得られた。
また、本処方を原液とし、適宜圧縮ガス（窒素、ＬＰＧ、炭酸等）を用いてエアゾール製品としてもよい。 An antiviral mist was obtained by discharging the skin external preparation of Formulation Example 1 using a mist-like dispenser.
Alternatively, this formulation may be used as a stock solution, and an aerosol product may be prepared by using a compressed gas (nitrogen, LPG, carbonic acid, etc.) as appropriate.
（処方例２）皮膚外用剤（ジェル）
配合成分 　　　　　　　　　　　　　　　　　　　　　　 質量％
エタノール　　　　　　　　　　　　　　　　　　　　　　３０．０
ハッカ油　　　　　　　　　　　　　　　　　　　　　　　０．０７
ローズマリー油　　　　　　　　　　　　　　　　　　　　０．０３２
セージ油 　　　　　　　　　　　　　　　　　　　　　　 ０．０２
ユーカリ油　　　　　　　　　　　　　　　　　　　　　　０．０３
（ＰＥＧ－２４０／デシルテトラデセス－２０／ＨＤＩ）
コポリマー　　　　　　　　　　　　　　　　　　　　　　０．５
カルボキシビニルポリマー　　　　　　　　　　　　　　　０．４５
２－アミノ－２－メチル－１，３－プロパンジオール 　　 ０．４
（アクリレーツ／アクリル酸アルキル(Ｃ１０－３０））
クロスポリマー　　　　　　　　　　　　　　　　　　　　０．０５
ポリクオタニウム－５１　　　　　　　　　　　　　　　　０．１
水　　　　　　　　　　　　　　　　　　　　　　　　　　残余
香料　　　　　　　　　　　　　　　　　　　　　　　　　０．１
合計　　　　　　　　　　　　　　　　　　　　　　　　　１００ (Formulation Example 2) Skin external preparation (gel)
Ingredient mass%
Ethanol 30.0
Mint oil 0.07
Rosemary oil 0.032
Sage oil 0.02
Eucalyptus oil 0.03
(PEG-240 / decyltetradeceth-20 / HDI)
Copolymer 0.5
Carboxyvinyl polymer 0.45
2-amino-2-methyl-1,3-propanediol 0.4
(Acrylates / alkyl acrylate (C10-30))
Crosspolymer 0.05
Polyquaternium-51 0.1
Water residual fragrance 0.1
Total 100
（処方例３）皮膚外用剤（ジェル）
配合成分　　　　　　　　　　　　　　　　　　　　　　　質量％
ヒドロキシプロピルセルロース　　　　　　　　　　　　　０．５
カチオン化デンプン　　　　　　　　　　　　　　　　　　１．０
水　　　　　　　　　　　　　　　　　　　　　　　　　　残余
合計　　　　　　　　　　　　　　　　　　　　　　　　　１００
（＊）センサマーＣＩ－５０ (Prescription Example 3) Skin external preparation (gel)
Ingredient mass%
Hydroxypropyl cellulose 0.5
Cationized starch 1.0
Water Total 100
(*) Sensormer CI-50
（処方例４）皮膚外用剤（ジェル）
配合成分　　　　　　　　　　　　　　　　　　　　　　　質量％
エタノール　　　　　　　　　　　　　　　　　　　　　　１０．０
ハッカ油 　　　　　　　　　　　　　　　　　　　　　　 ０．０７
ローズマリー油　　　　　　　　　　　　　　　　　　　　０．０３２
セージ油 　　　　　　　　　　　　　　　　　　　　　　 ０．０２
ユーカリ油　　　　　　　　　　　　　　　　　　　　　　０．０３
カルボキシビニルポリマー　　　　　　　　　　　　　　　０．５
水酸化カリウム　　　　　　　　　　　　　　　　　　　　０．２
グリセリン　　　　　　　　　　　　　　　　　　　　　　１０．０
ＰＥＧ－６０水添ヒマシ油　　　　　　　　　　　　　　　０．１
水　　　　　　　　　　　　　　　　　　　　　　　　　　残余
合計　　　　　　　　　　　　　　　　　　　　　　　　　１００ (Formulation Example 4) Skin external preparation (gel)
Ingredient mass%
Ethanol 10.0
Mint oil 0.07
Rosemary oil 0.032
Sage oil 0.02
Eucalyptus oil 0.03
Carboxyvinyl polymer 0.5
Potassium hydroxide 0.2
Glycerin 10.0
PEG-60 hydrogenated castor oil 0.1
Water Total 100

Claims (16)

  1. 有効成分として、ハッカ油、ユーカリ油、ローズマリー油、セージ油、ティーツリー油、月桃油、ペパーミント油、レモングラス油、カユプテ油、ニアウリ・シネオール油、ライム油、レモン油、レモンバーベナ油、セントジョーンズワート油、ラビンツァラ油、ローズウッド油、メリッサ/レモンバーム油、ミルラ油、マンダリン油、ベチバー油、フランキンセンス油、シトロネラ油、カルダモン油、アンジェリカ油、およびカチオン化デンプンからなる群から選択される１種または２種以上を含有することを特徴とするウイルス不活化剤。 As active ingredients, mint oil, eucalyptus oil, rosemary oil, sage oil, tea tree oil, moon peach oil, peppermint oil, lemongrass oil, cajeput oil, niau cineole oil, lime oil, lemon oil, lemon verbena oil, One selected from the group consisting of St. John's wort oil, Rabinzala oil, Rosewood oil, Melissa / Lemon balm oil, Myrrh oil, Mandarin oil, Vetiver oil, Frankincense oil, Citronella oil, Cardamom oil, Angelica oil, and cationized starch Or a virus inactivating agent comprising two or more.
  2. 有効成分として、ハッカ油、ユーカリ油、ローズマリー油、およびセージ油からなる群から選択される１種または２種以上を含有することを特徴とする、請求項１に記載のウイルス不活化剤。 The virus inactivating agent according to claim 1, wherein the virus inactivating agent comprises one or more selected from the group consisting of mint oil, eucalyptus oil, rosemary oil, and sage oil as the active ingredient.
  3. 有効成分として、ハッカ油、ユーカリ油、ローズマリー油、およびセージ油からなる群から選択される３種を含有することを特徴とする、請求項２に記載のウイルス不活化剤。 The virus inactivating agent according to claim 2, comprising three kinds of active ingredients selected from the group consisting of mint oil, eucalyptus oil, rosemary oil, and sage oil.
  4. 。
    有効成分として、ハッカ油、ユーカリ油、ローズマリー油、およびセージ油を含有することを特徴とする、請求項２に記載のウイルス不活化剤。     .
    The virus inactivating agent according to claim 2, wherein the active ingredient contains mint oil, eucalyptus oil, rosemary oil, and sage oil.
  5. リモネンの含有量が合計０．００６質量％以上である、請求項１から４のいずれか一項に記載のウイルス不活化剤。 The virus inactivating agent according to any one of claims 1 to 4, wherein a total content of limonene is 0.006% by mass or more.
  6. 有効成分として、カチオン化デンプンを含有することを特徴とする、請求項１に記載のウイルス不活化剤。 2. The virus inactivating agent according to claim 1, comprising a cationized starch as an active ingredient.
  7. カチオン化デンプンが、下記式（Ｉ）：
    Figure JPOXMLDOC01-appb-C000001
     ［式（Ｉ）中、Ｘ- は無機酸あるいは有機酸から誘導されるアニオンを示し；ａ、ｂは、ａ＋ｂ＝１としたとき、ａは０．６～０．９、ｂは０．４～０．１であり；平均分子量が３万～１００万である。］
    で表されるカチオン性ポリマーである、請求項１または６に記載のウイルス不活化剤。     The cationized starch has the following formula (I):
    Figure JPOXMLDOC01-appb-C000001
     [In the formula (I), X- represents an anion derived from an inorganic acid or an organic acid; a and b are a value of 0.6 to 0.9 when a + b = 1; ０．１0.1; the average molecular weight is 30,000-1,000,000. ]
    The virus inactivating agent according to claim 1, which is a cationic polymer represented by the following formula:
  8. カチオン化デンプンの平均分子量が１０万～５０万である、請求項１、６および７のいずれか一項に記載のウイルス不活化剤。 8. The virus inactivating agent according to claim 1, wherein the cationized starch has an average molecular weight of 100,000 to 500,000.
  9. カチオン化デンプンが塩化ヒドロキシプロピルトリモニウムデンプンである、請求項１および６から８のいずれか一項に記載のウイルス不活化剤。 9. The virus inactivating agent according to any one of claims 1 and 6 to 8, wherein the cationized starch is hydroxypropyltrimonium chloride starch.
  10. カチオン化デンプンの配合量が０．１質量％以上である、請求項１および６から９のいずれか一項に記載のウイルス不活化剤。 The virus inactivating agent according to any one of claims 1 and 6 to 9, wherein the amount of the cationized starch is 0.1% by mass or more.
  11. ウイルスがエンベロープを有する一本鎖ＲＮＡウイルスである、請求項１から１０のいずれか一項に記載のウイルス不活化剤。 The virus inactivating agent according to any one of claims 1 to 10, wherein the virus is a single-stranded RNA virus having an envelope.
  12. エンベロープを有する一本鎖ＲＮＡウイルスがオルトミクソウイルス科に属するウイルスである、請求項１１に記載のウイルス不活化剤。 The virus inactivating agent according to claim 11, wherein the single-stranded RNA virus having an envelope is a virus belonging to the orthomyxoviridae family.
  13. オルトミクソウイルス科に属するウイルスがインフルエンザウイルスである、請求項１２に記載のウイルス不活化剤。 The virus inactivating agent according to claim 12, wherein the virus belonging to the orthomyxoviridae is an influenza virus.
  14. 請求項１から１３のいずれか一項に記載のウイルス不活化剤を含むことを特徴とする皮膚外用剤組成物。 A skin external preparation composition comprising the virus inactivating agent according to any one of claims 1 to 13.
  15. アルコールをさらに含有することを特徴とする、請求項１４に記載の皮膚外用剤組成物。 The skin external preparation composition according to claim 14, further comprising an alcohol.
  16. アルコールの配合量が５０質量％以下である、請求項１５に記載の皮膚外用剤組成物。 The skin external preparation composition according to claim 15, wherein the blending amount of the alcohol is 50% by mass or less.
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